The objectives of this research proposal are to 1) Define the number of genes coding for Ia antigens and map them within the H-2 gene complex using new recombinants and antisera; 2) Decipher the complementing gene patterns which code for unique hybrid Ia antigens; 3) Identify the Ia specificities associated with functional subpopulations of T and B lymphocytes and non-lymphoid tissue; 4) Locate the Ia specificities on individual polypeptide chains of the molecule; 5) Test the hypothesis that one set of Ia molecules are involved in antigen presentation while a second set are involved in antigen recognition and generation of immune response. The expression of Ia in subpopulations of T cells and B cells would be performed by utilizing mutants with deficient immune functions. Sequential precipitation analysis and SDS electrophoresis techniques will be used to identify unique hybrid Ia molecules coded by complementing Ia genes and by xenoantisera. Specific anti-Ia sera and chemically isolated Ia molecules would be used as probes to determine the role of Ia antigens in immune response.